This phase II trial compares the effect of folate receptor alpha dendritic cells (FRαDCs) to placebo in treating patients with stage III or IV ovarian, fallopian tube or primary peritoneal cancer. FRαDCs, a dendritic cell vaccine, is made from a person's white blood cells. The white blood cells are treated in the laboratory to make dendritic cells (a type of immune cell) mixed with folate receptor alpha (FRalpha), a protein found in high levels on ovarian tumor cells. FRαDCs work by boosting the immune system to recognize and destroy the tumor cells by targeting the FRalpha protein on the tumor cell. Placebo is an inactive substance that looks the same as, and is given the same way as, the active drug or treatment being tested. The effects of the active drug are compared to the effects of the placebo. Giving FRαDCs may work better in preventing or delaying recurrence compared to placebo in patients with stage III or IV ovarian, fallopian tube, or primary peritoneal cancer.
PRIMARY OBJECTIVE: I. Compare recurrence-free survival (RFS) in advanced ovarian carcinoma (OC) patients vaccinated with multi-epitope folate receptor alpha-loaded dendritic cell vaccine (FRαDCs) (active vaccine) versus placebo. SECONDARY OBJECTIVES: I. Compare overall survival (OS) in advanced OC patients vaccinated with FRαDCs versus placebo. II. Compare the adverse event (AE) profile of FRαDCs with that of placebo. CORRELATIVE RESEARCH OBJECTIVES: I. Assess association of pre-existing immune microenvironment with RFS. II. Characterize the T cell and antibody responses to FRα and assess the association between the emergence of immunity and RFS. III. Assess for epitope spreading and evaluate the association between epitope spreading and RFS. IV. Compare archival tissue from surgery with post-recurrence biopsy tissue in those patients who develop recurrence to assess for common immune evasion mechanisms. V. Evaluate differences in ribonucleic acid (RNA) expression of FRαDCs and its association with RFS. OUTLINE: Patients are randomized to 1 of 2 arms. Randomization is 2:1, vaccine to placebo. ARM I: Patients may receive tetanus and diphtheria vaccine (Td) or tetanus-diphtheria-accellular pertussis vaccine (Tdap) intramuscularly (IM) prior to undergoing leukapheresis. Patients receive FRalphaDCs intradermally (ID) on day 1 of each cycle. Cycles repeat every 21 days for cycles 1-5 and then repeat every 91 days for cycles 6-12 in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo biopsy prior to apheresis and optionally at end of treatment, and blood sample collection, computed tomography (CT) and/or magnetic resonance imaging (MRI) throughout the study.f ARM II: Patients may receive Td or Tdap IM prior to undergoing leukapheresis. Patients receive placebo ID on day 1 of each cycle. Cycles repeat every 21 days for cycles 1-5 and then repeat every 91 days for cycles 6-12 in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo biopsy prior to apheresis and optionally at end of treatment, and blood sample collection, CT and/or MRI throughout the study. After completion of study treatment, patients are followed up every 3 months for up to month 36 then every 3 months until progression followed by every 6 months for up to year 8.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
TRIPLE
Enrollment
78
Undergo biopsy
Undergo blood sample collection
Undergo CT
Given IM
Undergo leukapheresis
Undergo MRI
Given ID
Given ID
Given IM
Mayo Clinic in Arizona
Scottsdale, Arizona, United States
RECRUITINGMayo Clinic in Florida
Jacksonville, Florida, United States
RECRUITINGMayo Clinic in Rochester
Rochester, Minnesota, United States
RECRUITINGRecurrence-free survival
Recurrence-free survival (RFS) will be compared inadvanced OC patients vaccinated with FRαDCs (active vaccine) versus placebo. RFS is defined as the time from study entry to either disease recurrence or death from any cause.
Time frame: Up to 8 years
Overall survival (OS)
Overall survival (OS) will be compared in advanced OC patients vaccinated with FRαDCs versus placebo. OS is defined as the time from study entry to death from any cause.
Time frame: Up to 8 years
Incidence of adverse events (AEs)
The maximum grade for each type of AE will be summarized using Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. The frequency and percentage of grade 3 and greater AEs will be compared between the 2 arms.
Time frame: Up to 30 days after last dose of study treatment
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